Immunobiology

Dienz Lab

Dr. Dienz studies the memory response to influenza virus infection and how it contributes to viral clearance and inflammation. Immunological memory protects against reinfection with the same pathogen and is often associated with the presence of neutralizing antibodies. Due to its high mutation rate, influenza virus is continuously evolving rendering antibodies generated during previous infections ineffective against new substrains. In addition, the emergence of new strains such as the recent H1N1 "swine flu" can cause pandemics with potentially high morbidity and mortality. While antibodies from previous infections are unable to neutralize the new virus, memory T cells recognize more conserved epitopes and may therefore offer protection even against new pandemic influenza strains. We previously described the pivotal role of the transcription factor NFAT in the effector functions of memory CD4 Tcells. We are now investigating how NFAT contributes to viral clearance and whether specific upregulation of NFAT in memory CD4 T cells may be a potential mechanism to enhance vaccine efficacy. Investigating the effector functions of memory CD4 T cells may also help in resolving the paradox that during an influenza pandemic especially young, healthy adults suffer from high morbidity and mortality. It is believed that an exuberant immune response in those individuals promotes excess inflammation and tissue damage. We are studying whether certain effector functions of memory CD4 T cells may contribute to this phenomenon. Since decreasing inflammation may reduce the severity of influenza virus infection, we are also investigating whether treatment with the vitamin A-derivative retinoic acid may reduce lung tissue damage. In a related project, we are collaborating with Drs. Mark Phillippe and Elizabeth Bonney in Ob-Gyn to elucidate the mechanisms responsible for the high mortality seen in pregnant women infected with influenza virus.